Saint John Chrysostom (center) in the midst of Saints Basil the Great and Gregory the Theologian.

He was born in Antioch of noble parents: his father was a high-ranking military officer. His father died soon after his birth and so he was brought up by his mother Anthusa. He was baptized in 370 and tonsured a reader (one of the minor orders of the Church). He began his education under a pagan teacher named Libanius, but went on to study theology under Diodore of Tarsus (one of the leaders of the later Antiochian School) while practising extreme asceticism. He was not satisfied, however, and became a hermit (circa 375) and remained so until poor health forced a return to Antioch.

He was then ordained a deacon in 381 by St. Meletius of Antioch, and was ordained a presbyter in 386 by Bishop Flavian I of Antioch. It seems this was the happiest period of his life. Over about twelve years, he gained much popularity for the eloquence of his public speaking. Notable are his insightful expositions of Bible passages and moral teaching. The most valuable of his works are his Homilies on various books of the Bible. He particularly emphasized almsgiving. He was also most concerned with the spiritual and temporal needs of the poor. He spoke out against abuse of wealth and personal property. In many respects, the following he amassed was no surprise. His straightforward understanding of the Scriptures (in contrast to the Alexandrian tendency towards allegorical interpretation) meant that the themes of his talks were eminently social, explaining the Christian's conduct in life.

One incident that happened during his service in Antioch perhaps illustrates the influence of his sermons best. Around the time he arrived in Antioch, the bishop had to intervene with the Emperor St. Theodosius I on behalf of citizens who had gone on a riotous rampage in which statues of the Emperor and his family were mutilated. During the weeks of Lent in 387, John preached 21 sermons in which he entreated the people to see the error of their ways. These apparently had a lasting impression on the people: many pagans reportedly converted to Christianity as a result of them. In the event, Theodosius' vengeance was not as severe as it might have been, merely changing the legal standing of the city.

In late October of 397, he was called (somewhat against his will) to be the bishop of Constantinople. He deplored the fact that Imperial court protocol would now assign to him access to privileges greater than the highest state officials. During his time as bishop he adamantly refused to host lavish entertainments. This meant he was popular with the common people, but unpopular with the wealthy and the clergy. In a sermon soon after his arrival he said, "people praise the predecessor to disparage the successor." His reforms of the clergy were also unpopular with these groups. He told visiting regional preachers to return to the churches they were meant to be serving—without any pay out.

His time there was to be far less at ease than in Antioch. Theophilus, the Pope of Alexandria, wanted to bring Constantinople under his sway and opposed John's appointment to Constantinople. Being an opponent of Origen's teachings, he accused John of being too partial to the teachings of that master. Theophilus had disciplined four Egyptian monks (known as "the Tall Brothers") over their support of Origen's teachings. They fled to and were welcomed by John. He made another enemy in Aelia Eudoxia, the wife of the eastern Emperor Arcadius, who assumed (perhaps with justification) that his denunciations of extravagance in feminine dress were aimed at herself.

St. John was fearless when denouncing offences in high places. An alliance was soon formed against him by Eudoxia, Theophilus and other enemies of his. They held a synod in 403 to charge John, in which the accusation of Origenism was used against him. It resulted in his deposition and banishment. He was called back by Arcadius almost immediately, however, for the people of the city were very angry about his departure. There was also a "quaking" in the Imperial bedroom (thought to be either an actual earthquake or perhaps as a stillbirth or miscarriage for the empress) which was seen as a sign of God's anger. Peace was shortlived. A silver statue of Eudoxia was erected near the cathedral of Hagia Sophia. John denounced the dedication ceremonies. He spoke against her in harsh terms: "Again Herodias rages; again she is confounded; again she demands the head of John on a charger" (an allusion to the events surrounding the death of John the Forerunner). Once again he was banished, this time to Caucasus in Georgia.

The pope in Rome (Innocent I at this time) protested at this banishment, but to no avail. John wrote letters which still held great influence in Constantinople. As a result of this, he was further exiled to Pityus (on the eastern edge of the Black Sea). However, he never reached this destination, as he died during the journey. His final words were